Systemic inflammatory response syndrome (SIRS) is a systemic inflammatory state enhanced due to excessive release of a substance such as cytokine triggered by infection or the like. Eighteen million people die of this disease every year in the world, but there has been no effective therapy for it.
Although clinical trials for an anti-TNF-α antibody, IL-1Ra, and the like have so far been attempted in order to neutralize an excessively produced inflammatory cytokine in diseases accompanied with SIRS, they have not yet succeeded in certifying their effectiveness.
The reason why an attempt to treat SIRS using a single inflammatory cytokine as a target has not yet produced effective results is presumed because SIRS has various backgrounds or symptoms and not only one cytokine but also a very complicated cytokine network causes SIRS.
Therapeutic apheresis, such as blood filtration, for comprehensively removing substances that cause disease from the blood have conventionally attracted attentions and a technology of removing proteins including cytokines of a middle molecular weight range has been proposed. For example, there is an attempt of using therapeutic apheresis by filtration/dialysis to remove all the mediators involved in a complicated cytokine network. Effectiveness produced by a mechanism different from monoclonal antibody administration of a cytokine to multiple organ failure is considered but there is a limit to the amount removable by it.
There have recently been reports on an inflammatory cytokine adsorbent developed to remove from the blood these inflammatory cytokines adsorbed thereto to treat SIRS (refer to, for example, Patent Document 1).
Furthermore, study results showing that histones are very important as a substance that causes SIRS have recently been disclosed newly (refer to, for example, Non-patent Documents 1 and 2).
This can be verified from the facts that the blood histone level of SIRS patients is several ten times to several hundred times higher than that of the normal subjects and that inflammatory model mice recovered by the administration of a histone antibody (refer to, for example, Non-patent Document 3).
Histones are main proteins that constitute chromatin found in eukaryotes. Due to abundant basic proteins, they are charged with a positive charge. Histones allow deoxyribonucleic acid (DNA) having negative charges derived from a phosphoric acid group to wrap around them about 2 times and play a role of packaging folded long DNA molecules in their nuclei. Histones are classified into four families, that is, H2A, H2B, H3, and H4. A histone octamer consisting of two copies of each of these four histones and wrapped by DNA is called “nucleosome”. On the other hand, histones to be bound to DNA between nucleosomes (linker DNA) are called “linker histones” and a typical one is called Histone H1.
These histones are known to be cationic and in fact, as disclosed in Patent Documents 2 and 3, they are target proteins to be removed by a basic adsorbent such as sulfated cellulose or hydroxyapatite.